The treatment of chronic wounds has continually been a challenge to the medical profession. It is often very difficult to achieve wound healing in patients, and health professionals have resorted to managing wounds rather than being able to achieve healing and recovery.
Eyes are subject to chronic wounds and there have been prior attempts in the art to address these problems. Corneal epithelial defects generally heal within 24 to 48 hours. However, certain conditions can predispose the cornea to delayed healing or even continuous epithelial breakdown. For example, in photo refractive keratectomy (PRK) the cornea typically takes five to seven days to reepithelialize. Subepithelial haze occurs more commonly in patients with slower reepithelialization, and patients with decreased corneal sensation due to cranial nerve V.sub.I dysfunction suffer from persistent corneal epithelial defects that often lead to blindness. Patients who undergo penetrating keratoplasty often have difficulty with reepithelialization of the cornea. Reepithelialization of the cornea can be enhanced by patching of the eye and by providing adequate lubrication for the cornea in the form of drops and ointment. Many topical agents can delay or be toxic to the corneal epithelium. Numerous pharmacologic therapies have been advocated (sodium citrate and collagenase inhibitors) as enhancing reepithelialization of the cornea; however, success has been limited.
With regard to chronic wounds on areas of the body other than the eye, there is often associated microvascular disease i.e. poor vascular supply. Patients then suffer from poor oxygen flow to the tissues. It has been found that oxygen treatment in a hyperbaric oxygen chamber does provide for enhancement of healing. Decubitus ulcers, also known as pressure sores or bedsores, have classically been thought to be due to pressure on bony prominences of the body decreasing blood supply to the overlying skin, resulting in epithelial breakdown. This is especially common on the sacral area and buttocks. Decubitus ulcers are managed by preventing pressure in the areas prone to breakdown by turning the bedridden patient at regular intervals and by removing any toxic substance (eg. urine) from the particular area affected. There are other wounds as well which are reportedly caused by vascular problems, and recommended treatment has been to surgically revascularize the tissues. Little consideration is given to the role of sensory loss and its effect on maintaining an intact epithelium.
Other previously described methods of treating wounds have focussed on the use of epidermal growth factor (EGF), transforming growth factor (TGF), and fibroblast gowth factor (FGF). TGF binds to the same cell surface receptor as EGF. For treatment methods using EGF, see, e.g., PCT WO 86/02271 and EP 0140 998. EP 190 018 describes the use of TGF for the treatment of epithelial wounds and stromal wounds. These agents have turned out to be relatively ineffective in the management of chronic wounds.
U.S. Pat. No. 4,287,184 to Young describes using a form of NGF having a molecular weight of 116,000, in an experiment to heal a skin wound in mice. Refering to his invention, Young states that "the wound healing effect of the NGF of this invention is not observed with other forms of NGF, eg. 2.5S NGF." [col. 3, lines 44-46].
Despite the attempts to manage chronic wounds, to date no treatment is universally effective. Patients that do not respond to conventional therapies over long periods of time may suffer from continued chronic breakdown. In addition, the conventional therapies may require considerable periods of therapy, resulting in patients being without eyesight or being disabled due to chronic wounds for extended periods of time. Finally, the popularity of new eye operations designed to correct vision defects have resulted in a new population of eye patients who will need to undergo periods of recovery from epithelial disruption.
Thus, there remains a need for a more effective method for treating chronic wounds which will aid wound healing in the eye and and in other areas of the body.
The present invention satisfies this need and provides other advantages as well.